Adenosine receptors have been divided into two subtypes, based on adenylate cyclase activity: A.sub.1 (R.sub.i) receptors mediate inhibition and A.sub.2 (R.sub.a) receptors mediate stimulation of adenylate cyclase activity. Some N.sup.6 -substituted adenosine analogs, like N.sup.6 -R-phenyl isopropyl adenosine (R-PIA) have very high affinity for A.sub.1 adenosine receptors, but at A.sub.2 receptors 5'-N-ethylcarboxamido-adenosine (NECA) is more potent than N.sup.6 -substituted analogs. Alkylxanthines, such as caffeine and theophylline, are the best known antagonists at adenosine receptors.
Adenine was generally believed to have no effect on adenosine receptor-controlled systems. However, it was found that at low concentrations adenine displays specific competitive antagonism of adenosine-induced cyclic Amp accumulation in a human fibroblast cell line. Methylation of adenine at the 9-position increases potency about 4-fold in this assay. At higher concentration, both compounds show nonspecific inhibitory activity.